What Is Cushing's Syndrome? What Causes Cushing's Syndrome?

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Main Category: Endocrinology
Also Included In: Obesity / Weight Loss / Fitness
Article Date: 02 Dec 2009 - 7:00 PDT

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Cushing's syndrome, or Cushing syndrome is a collection of signs and symptoms caused by too much cortisol hormone. It is a very complex hormonal condition which affects many parts of the body. The most common signs and symptoms include thinning of the skin, weight gain, bruising, high blood pressure, osteoporosis, diabetes, puffed up face, weakness, and in females, interruption of menstrual periods.

High levels of blood cortisol may be caused by large doses of steroid medication prescribed for other illnesses, such as asthma. Some patients may have a disorder that causes their body to produce excess steroid hormone cortisol.

Cortisol is the primary stress hormone - it is the major natural GC (GLUCOCORTICOID) in humans. Cortisol is produced by the adrenal glands, which are located just above the kidneys. Cortisol regulates body glucose levels, as well as suppressing the immune system.

According to Medilexicon's medical dictionary:

"a disorder resulting from increased adrenocortical secretion of cortisol (giving clinical picture of Cushing disease), due to any one of several sources: ACTH-dependent adrenocortical hyperplasia or tumor, ectopic ACTH-secreting tumor, or excessive administrations of steroids; characterized by trunkal obesity, moon face, acne, abdominal striae, hypertension, decreased carbohydrate tolerance, protein catabolism, psychiatric disturbances, and osteoporosis, amenorrhea, and hirsutism in females; when associated with an ACTH-producing adenoma, called Cushing disease."

Cushing's syndrome was described by Dr. Harvey Cushing (1869-1939) in 1932. Dr. Cushing was an American neurosurgeon and a pioneer of brain surgery.

What are the symptoms of Cushing's syndrome?

A symptom is something the patient feels and reports, while a sign is something other people, such as the doctor detect. For example, pain may be a symptom while a rash may be a sign.

As Cushing's syndrome can affect various parts of the body, its signs and symptoms may differ considerably from patient to patient.

• Weight gain - the hallmark sign of Cushing's syndrome is accelerated weight gain. Weight gain is more pronounced on the chest, stomach and face areas. Elevated levels of cortisol cause fat to be redistributed to those areas.


• Thin limbs - the patient's arms and legs appear thin compared to the rest of the body.


• Buffalo hump - deposits of fat accumulate on the back of the neck and shoulders, giving what is known as a buffalo hump.


• Face - the face becomes puffy, rounded and red.


• Skin:
  
  
  • Skin becomes very thin
  • Skin bruises easily
  • Reddish-purplish stretch marks appear on the stomach, buttocks, limbs, and breasts.
  • Spots develop on the shoulders, chest and face
  • Acanthosis - the skin in the neck area darkens
  • Edema - water retention under the skin
  • Profuse sweating
  • Women may have excessive facial and body hair (hirsutism)
  • Women may lose hair on their head
  • Skin lesions take a long time to heal, such as grazes, cuts, scratches and insect bites


• Muscles - muscles in the shoulders, limbs and hips may weaken


• Bones - elevated levels of cortisol can lead to osteoporosis (brittle bones). Patients are more vulnerable to fractures; even when carrying out normal daily tasks, such as lifting.


• Psychological changes - excess cortisol can lead to psychological problems and mood changes, including:
  
  
  • Anxiety
  • Depression
  • Irritability
  • Loss of emotional control
  • Panic attacks


• Menstruation - periods may become irregular, less frequent, and sometimes completely stop.


• Sexual problems - males may have a much lower libido (sex drive). Erectile dysfunction (inability to get or sustain an erection) and infertility are also possible among males. On the other hand, some patients may go the other way - their adrenal glands may overproduce testosterone and other hormones, leading to increased libido.


• Headaches


• Hypertension (high blood pressure)


• Excessively high blood glucose levels


• Increased thirst


• More frequent urination

If you have been prescribed corticosteroid drugs for the treatment of asthma, arthritis or inflammatory bowel disease and you experience Cushing's syndrome signs and symptoms, tell your doctor as soon as possible.

What are the causes of Cushing's syndrome?

Our endocrine system consists of a group of glands that work together and secrete many types of different hormones that regulate the body. The endocrine system includes the following glands - adrenal glands, pituitary gland, thyroid gland, parathyroid glands, pancreas, ovaries (in females) and testicles (in males).

Cortisol - cortisol, a hormone, is produced in the adrenal glands. Cortisol helps regulate blood pressure, as well as maintaining good cardiovascular function. Cortisol is also key in how our bodies respond to stress. The way our bodies metabolize (convert) proteins, carbohydrates and fat (from food) into energy is regulated by cortisol. When levels of cortisol rise too high the patient can develop Cushing's syndrome.

Exogenous Cushing's syndrome

• Corticosteroids - Exogenous Cushing's Syndrome occurs when the source (origin) is from outside the patient's body. If a patient takes high doses of corticosteroid drugs for a long time they have a higher risk of developing Cushing's syndrome. Examples of medications include prednisone, dexamethasone (Decadron) and methylprednisolone (Medrol) - they have the same effect on our bodies as cortisol has.
  
  Corticosteroids are prescribed for rheumatoid arthritis, lupus, asthma, and for recipients of organ transplants. As doses may need to be fairly high to be effective, they may eventually have the same effects as excessive cortisol in our bodies.
  
  Injectable corticosteroids, used for joint pain, back pain and bursitis, may also cause the development of Cushing's disease.
  
  Some steroid creams, such as those used for eczema, as well as some inhaled steroids used for asthma, are not linked to a higher incidence of Cushing's syndrome; unless the dosages are extremely high.

Endogenous Cushing's Syndrome

When Cushing's syndrome is caused by the body's excess production of cortisol it is called Endogenous Cushing's Syndrome. The overproduction may be due to just one or both adrenal glands. In some cases there may be an overproduction of ACTH (adrenocorticotropic hormone) which regulates cortisol production. In such cases Cushing's syndrome may be associated with:

• A tumor in the pituitary gland - this is benign (non-cancerous) tumor of the pituitary gland. The pituitary gland is at the base of the brain and secrets ACTH. ACTH stimulates cortisol production from the adrenal gland. If the pituitary gland produces too much ACTH, the result will be too much cortisol.


• An ectopic ACTH-secreting tumor - the tumor itself may starts secreting ACTH (rare). The tumor may be in the pancreas, thyroid, thymus gland or lung. The tumor may be benign or malignant.


• Disorder of the adrenal gland(s) - an adrenal adenoma (non-cancerous tumor of the adrenal cortex) may result in overproduction of cortisol.

Diagnosis of Cushing's syndrome

Cushing's syndrome is rare. It is not uncommon for a person to have signs and symptoms but not have Cushing's syndrome - many of the symptoms of Cushing's syndrome may appear in other medical conditions and diseases. A good doctor needs to eliminate other possible conditions and diseases before diagnosing Cushing's syndrome.

The patient will be examined by a GP (general practitioner, primary care physician), and will probably be referred on to a doctor who specializes in hormone disorders - an endocrinologist. The diagnosis will be made after examining the patient's medical history, interviewing the patient, examining the patient, and ordering some tests and scans.

Tests may include:

• Urine test - urine samples are collected over a 24-hour period and tested for levels of cortisol. Patients with Cushing's syndrome have constantly high levels of cortisol in their urine.


• Blood tests - similarly, samples are collected over a 24-hour period. Most people's cortisol levels drop during the night, but not if the patient has Cushing's syndrome.


• Saliva tests - among healthy patients cortisol levels fluctuate throughout the day, and drop significantly during the night. However, cortisol levels of patients with Cushing's syndrome do not drop during the night.


• Low-dose dexamethasone suppression test - the patient takes dexamethasone, a steroid tablet, every six hours for a total of 48 hours. Urine samples are taken before, during and after taking tablets. Dexamethasone stops cortisol production, except when the patient has Cushing's syndrome.

After diagnosis - identifying the cause

As soon as a patient has been diagnosed with Cushing's syndrome, further tests will be ordered to try to find out what caused the elevated levels of cortisol.

• CRH (Corticotropin-releasing hormone stimulation test) - the patient receives a CRH injection. If ACTH and cortisol levels subsequently rise, it is probably due to a tumor in the pituitary gland. If levels do not rise, most likely the syndrome is caused by a tumor in the adrenal gland, or somewhere else.


• High-dose dexamethasone suppression test - a higher dose of dexamethasone is administered. If blood cortisol levels drop it is probably due to a tumor in the pituitary gland, if not it may be due to a tumor somewhere else.


• Imaging scans - a CT (computerized tomography) or MRI (magnetic resonance imaging) scan can detect the presence of a tumor in the adrenal or pituitary glands. In some cases a tumor may not be detected, even with scans.


• Petrosal sinus sampling - a blood sample from the petrosal sinuses - veins that come from the pituitary gland - is taken. ACTH blood levels are compared to samples taken from the forearm. If blood samples from the petrosal sinuses have higher ACTH levels, most likely this is because of a tumor in the pituitary gland. If levels are the same or similar, there is probably a tumor somewhere else in the body.

Diagnosing Cushing's syndrome may take some time, because tests and scans may have to be done again. Some patients may be prescribed metyrapone until a diagnosis is made. Metyrapone lowers the amount of cortisol. Patients taking metyrapone will be monitored in hospital. Some patients may also have to undergo a bone mineral density test.

What are the treatment options for Cushing's syndrome?

Treatment is aimed at bringing down cortisol levels. Treatment options depend on several factors, including the cause of the syndrome.

• Corticosteroid use - Patients on long-term high dosage corticosteroids may have their dosages gradually reduced. It is important that the dosage lowers enough to bring down cortisol levels, while at the same time still effectively treating the asthma, arthritis or other condition. The patient may be prescribed a non-corticosteroid medication.
  
  Patients must not lower corticosteroid dosages on their own. A sudden drop or stop of corticosteroid drugs may result in dangerously low levels of cortisol.


• Surgery - sometimes the surgical removal of a tumor is recommended. A pituitary tumor may be removed through the patient's nose. Tumors in the adrenal glands, pancreas or lungs may be removed with conventional surgery, or keyhole surgery (laparoscopic surgery, or minimally invasive surgery).
  
  After surgery patients will need to take cortisol replacement drugs. Eventually, as the adrenal hormone production returns, the doctor will taper down the cortisol replacement drugs (wean the patient off them).


• Radiotherapy (radiation therapy) - this may be used as well as surgery if the surgeon cannot remove the tumor completely. Some patients who are not suitable surgery candidates may receive radiation therapy in small doses over a number of weeks. Sometimes the radiation is administered as a single treatment.


• Chemotherapy - if the syndrome is caused by a cancerous tumor, such as a lung tumor, the doctor may recommend chemotherapy. Drugs are injected which destroy cancer cells.


• Drugs - if surgery or radiation are not effective enough, the doctor may prescribe medications to control excessive production of cortisol. Examples include ketoconazole (Nizoral), mitotane (Lysodren) and metyrapone (Metopirone). If a tumor causes low hormone production, the doctor may prescribe HRT (hormone replacement therapy).

Surgical removal of the adrenal gland - if none of the treatments works properly the doctor may recommend a bilateral adrenalectomy (surgically removing the adrenal glands).

Cushing's syndrome is a serious condition and can lead to death if left untreated.

What are the complications of Cushing's syndrome?

If the syndrome is left untreated the following complications may occur:

• Osteoporosis - bone loss
• Hypertension - elevated blood pressure (high blood pressure)
• Kidney stones
• Diabetes
• More frequent infections
• Greater risk of unusual infections
• Loss of muscle mass
• Loss of strength

Written by Christian Nordqvist
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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